Novel Glutathione Leads to Longer Ovarian Cancer Survival

Novel Glutathione Leads to Longer Ovarian Cancer Survival

NEW YORKPreviously treated patients with ovarian cancer who received a
novel glutathione (TLK286, Telik, Inc., San Francisco) have thus far survived
a median of more than 56 weeks, according to preliminary results from an
ongoing multicenter phase II trial. John J. Kavanagh, MD, presented the
results at the Mount Sinai School of Medicine Chemotherapy Foundation
Symposium XX.

Final median survival has not yet been reached in the trial, which
includes patients who are receiving TLK286 as second-, third- or fourth-line
therapy. Historically, ovarian cancer patients receiving second-line
liposomal doxorubicin (Doxil) or topotecan (Hycamtin) in clinical trials had
median survival rates of 36 and 41 weeks, respectively, said Dr. Kavanagh,
professor of medicine, Department of Gynecologic Medical Oncology, M.D.
Anderson Cancer Center.

"Median survival with TLK286 is strikingly longer" and increasing, Dr.
Kavanagh said. "Response rate is similar, with complete responses seen in
this study, and a toxicity profile and dosage reduction very favorable,
compared to those therapies."

Responses in the 36-patient trial include one complete remission of more
than 14 months’ duration, Dr. Kavanagh said. In addition, there have been
four partial responses associated with improvement of symptoms.

The novel cytotoxic agent is given intravenously in an inactive form. In
cancer cells, it is activated by an enzyme (glutathione S-transferase P1-1)
expressed in ovarian cancer and other solid tumors.

Phase I data are "extensive" for TLK-286, with a large number of patients
receiving multiple courses, Dr. Kava-nagh said. There is a safety database
representing approximately 1,500 courses in at least 320 previously treated
patients who received the new agent on an every-3-week or weekly schedule.
Side effects have been mild and reversible.

Investigators have noticed durable responses in multiple bulky tumors, he
said. The overall response rate was about 15% (1 complete response and 4
partial responses), and the disease control rate was 50% (the 5 responders
plus 12 with stable disease). Likelihood of response did not seem to vary
according to number of prior regimens or by whether their disease was
platinum resistant or platinum refractory. "Responses were seen in all
subgroups and at all centers," Dr. Kavanagh said.